ECIG24: Effect of the Electronic Cigarette on Withdrawal Symptoms

• Sponsor: Queen Mary University of London (Other)
• Overall Status: Completed
• CT.gov ID: NCT01454362
• Collaborator: (none)
• Enrollment: 51
• Location: 1
• Arms: 2
• Duration (Months): 1.9
• Patients Per Site Per Month: 26.3

Study Details

Study Description

Brief Summary

Study rationale: Sensory/behavioural elements of smoking play a role in smoking behaviour and may have a potential to assist smoking cessation. Among current treatments for smokers, only the nicotine inhalator is attempting to address such factors. The inhalator's efficacy does not exceed that of the other nicotine replacement therapy (NRT) products, but it mimics the relevant sensory input to only a limited extent, and its nicotine delivery is dependent on intensive puffing. Recently a new product, the Electronic Cigarette (E-C) has become available, which provides a more realistic behaviour and sensory replacement for smoking and can provide good nicotine levels with less effort.

Primary objective: To compare E-C and nicotine inhalator in their effects on tobacco withdrawal symptoms over 24hr abstinence.

Hypotheses: E-C will be more effective than the inhalator in reducing withdrawal symptoms and craving and elicit more favorable user ratings. It will also provide higher nicotine levels.

Study design: In a cross-over study, participants will be randomized to the sequence of conditions and provide baseline measures and samples for salivary cotinine analysis. They will be asked to abstain from smoking their usual cigarettes and use the allocated product over 24 hours. They will return to the study centre the following day, and complete measures of craving and withdrawal, ratings of subjective and sensory effects of the products, product satisfaction, and adverse effects. They will also provide saliva samples for cotinine analysis. Abstinence from smoking will be verified with CO readings.

Condition or Disease	Intervention/Treatment	Phase
Mental and Behavioral Disorders; Withdrawal State	Drug: Nicotine	N/A

Detailed Description

There is considerable interest in E-Cs at the moment and the study would provide information on whether the E-C surpasses the tried and tested nicotine inhalator. If so, it would open a possibility of its utilization in smoking cessation, and provide encouragement for further examination of the role of sensorimotor replacements in the treatment of tobacco dependence.

Study Design

• Study Type: Interventional
• Actual Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Phase 4 Study to Compare of the Effects of the Electronic Cigarette and Nicotine Inhalator on Tobacco Withdrawal Symptoms Over 24 Hours of Abstinence
• Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Electronic cigarette We analysed 15 brands of the most popular E-Cs in the UK, EU and US for nicotine levels in the mist. Vapours were generated from cartridges of various nicotine content using a standard single-port linear smoking machine with a puff volume of 70 ml, 1 puff every 7 sec., and a puff duration of 1.8 sec (based on averaged puffing conditions from 10 E-C users found during preliminary studies). Nicotine was absorbed in two sequential washing bottles with methanol and internal standards and analysed with gas chromatography. One brand was selected for this study as it consistently delivers about 1mg of nicotine with 20 puffs.	Drug: Nicotine; Inhalation of nicotine.; Other Names: Nicorette inhalator
Active Comparator: Nicotine Inhalator The inhalator consists of a nicotine cartridge which is placed into a plastic mouthpiece. One cartridge contains 10mg of nicotine of which 4mg of nicotine can be extracted. Nicotine is delivered mainly through the oral cavity, throat, and upper respiratory tract with a minor fraction reaching the lungs. A single cartridge can be used for one 20-minute period of continuous puffing or periodic use of up to 400 puffs per cartridge.	Drug: Nicotine; Inhalation of nicotine.; Other Names: Nicorette inhalator

Outcome Measures

Primary Outcome Measures

1. Comparison of E-C and Inhalator in Effects on Withdrawal Over 24 Hours of Use. [24 hours]

   Mood and Physical Symptoms Scale (MPSS): Measure of severity of urges to smoke and tobacco withdrawal symptoms. A five-point scale is used to rate 'How much of the time have you felt the urge to smoke in the past week?' ((1) 'not at all' to (5) 'almost all of the time') and 'How strong have the urges been?' ('no urges' to 'very strong'). Clients also rate depression, irritability, restlessness, hunger, poor concentration, poor sleep at night, and anxiety during the past week ((1)=not at all to (5)=extremely). The combined score to questions on depression, irritability, restlessness, hunger, and poor concentration are averaged to give the MPSS score. A higher score means a more severe rating of withdrawal. The primary outcome is a change in MPSS score between baseline and 24 hours (value at 24 hours minus value at baseline). Therefore, a smaller change in MPSS score represents a smaller increase in tobacco withdrawal symptoms.

Secondary Outcome Measures

1. Change in Salivary Cotinine Levels After 24-hour Use. [24 hours]

   Cotinine is a measure sensitive enough to detect effects of a switch to different nicotine products and salivary cotinine was shown to be dependent on nicotine mouth exposure. The results show the mean change in salivary cotinine in each study arm (all study participants).

2. Reinforcing Effects of Smoking [24 hours]

   Modified Cigarette Evaluation Questionnaire (mCEQ): Measure of reinforcing effects of smoking (pleasant feeling). Mean pleasant feeling from using product (rating 0-4). Higher value indicating the higher rating of pleasure.

3. Airway Sensations [24 hours]

   Sensory effects: Measure of airway sensations (throat and chest). Mean enjoyment score (rating 0-4), higher the score indicating increased enjoyment.

4. Product Satisfaction [24 hours]

   Product satisfaction: Ratings of product satisfaction (when compared to cigarettes). Rating 0-4, with higher value indicating higher satisfaction ratings.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Volunteers smoking at least 12 cigarettes per day

• First cigarette smoked within 60 minutes of waking up

• Willing to abstain from smoking for one day in 2 consecutive weeks.

Exclusion Criteria:

• Under 18 years of age

• Current psychiatric illness

• Pregnant or breastfeeding

• Enrollment in other research projects

• Used electronic cigarette and/or nicotine inhalator before

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tobacco Dependence Research Unit	London		United Kingdom	E1 2JH

Sponsors and Collaborators

• Queen Mary University of London

Investigators

• Principal Investigator: Hayden J McRobbie, PhD, Queen Mary University of London

Study Documents (Full-Text)

None provided.

More Information

Publications

• Cappelleri JC, Bushmakin AG, Baker CL, Merikle E, Olufade AO, Gilbert DG. Multivariate framework of the Brief Questionnaire of Smoking Urges. Drug Alcohol Depend. 2007 Oct 8;90(2-3):234-42. Epub 2007 May 7.
• Rose JE, Behm FM, Westman EC, Bates JE, Salley A. Pharmacologic and sensorimotor components of satiation in cigarette smoking. Pharmacol Biochem Behav. 2003 Sep;76(2):243-50.
• West R, Hajek P. Evaluation of the mood and physical symptoms scale (MPSS) to assess cigarette withdrawal. Psychopharmacology (Berl). 2004 Dec;177(1-2):195-9. Epub 2004 Jun 4.
• West RJ, Hajek P, Belcher M. Severity of withdrawal symptoms as a predictor of outcome of an attempt to quit smoking. Psychol Med. 1989 Nov;19(4):981-5.

• Responsible Party: Hayden McRobbie, Reader in Public Health Interventions, Queen Mary University of London
• ClinicalTrials.gov Identifier: NCT01454362
• Other Study ID Numbers: QMUL111111; 2011-005565-20; U1111-1127-4445
• First Posted: Oct 19, 2011
• Last Update Posted: Mar 27, 2019
• Last Verified: Mar 1, 2019

• Keywords provided by Hayden McRobbie, Reader in Public Health Interventions, Queen Mary University of London: nicotine; inhalator; electronic cigarette; tobacco
• Additional relevant MeSH terms: Substance Withdrawal Syndrome; Nicotine

Study Results

Participant Flow

Recruitment Details	Participants were recruited at the Tobacco Dependence Research Unit in London between January 2013 and February 2013.
Pre-assignment Detail	Inclusion Criteria Smoking at least 12 cigarettes per day; first cigarette smoked within 60 mins of waking; willing to abstain from smoking for one day in 2 consecutive weeks. Exclusion Criteria Under 18s; current psychiatric illness; planning pregnancy, pregnant or breastfeeding; enrolled in other research; used EC or inhaler before.

Arm/Group Title	Electronic Cigarette Then, Nicotine Inhalator	Nicotine Inhalator Then, Electronic Cigarette
Arm/Group Description	Randomised to receive electronic cigarette at the first session. Tested at study session then given to use ad-lib over 24 hours. Participants then returned to the clinic. 1 week wash out period. Asked to return to clinic to receive Nicotine Inhalator. Tested at clinic then given product to use ad-lib over 24 hours. Participants then returned to the clinic. Nicotine: Inhalation of nicotine.	Randomised to receive Nicotine Inhalator at the first session. Tested at study session then given to use ad-lib over 24 hours. Participants then returned to the clinic. 1 week wash out period. Asked to return to clinic to receive electronic cigarette. Tested at clinic then given product to use ad-lib over 24 hours. Participants then returned to the clinic.
Period Title: Overall Study
STARTED	28	23
COMPLETED	28	23
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Electronic Cigarette First, Then Nicotine Inhalator	Nicotine Inhalator First, Then Electronic Cigarette	Total
Arm/Group Description	Randomised to receive electronic cigarette at the first session. Tested at study session then given to use ad-lib over 24 hours. Participants then returned to the clinic. 1 week wash out period. Asked to return to clinic to receive Nicotine Inhalator. Tested at clinic then given product to use ad-lib over 24 hours. Participants then returned to the clinic.	Randomised to receive Nicotine Inhalator at the first session. Tested at study session then given to use ad-lib over 24 hours. Participants then returned to the clinic. 1 week wash out period. Asked to return to clinic to receive electronic cigarette. Tested at clinic then given product to use ad-lib over 24 hours. Participants then returned to the clinic.	Total of all reporting groups
Overall Participants	28	23	51
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	26 92.9%	22 95.7%	48 94.1%
>=65 years	2 7.1%	1 4.3%	3 5.9%
Sex: Female, Male (Count of Participants)
Female	5 17.9%	4 17.4%	9 17.6%
Male	23 82.1%	19 82.6%	42 82.4%

Outcome Measures

1. Primary Outcome

Title	Comparison of E-C and Inhalator in Effects on Withdrawal Over 24 Hours of Use.
Description	Mood and Physical Symptoms Scale (MPSS): Measure of severity of urges to smoke and tobacco withdrawal symptoms. A five-point scale is used to rate 'How much of the time have you felt the urge to smoke in the past week?' ((1) 'not at all' to (5) 'almost all of the time') and 'How strong have the urges been?' ('no urges' to 'very strong'). Clients also rate depression, irritability, restlessness, hunger, poor concentration, poor sleep at night, and anxiety during the past week ((1)=not at all to (5)=extremely). The combined score to questions on depression, irritability, restlessness, hunger, and poor concentration are averaged to give the MPSS score. A higher score means a more severe rating of withdrawal. The primary outcome is a change in MPSS score between baseline and 24 hours (value at 24 hours minus value at baseline). Therefore, a smaller change in MPSS score represents a smaller increase in tobacco withdrawal symptoms.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Reporting group

Arm/Group Title	Electronic Cigarette	Nicotine Inhalator
Arm/Group Description	All study participants.	All study participants.
Measure Participants	51	51
Mean (Standard Deviation) [units on a scale]	0.73 (0.64)	0.86 (0.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Electronic Cigarette, Nicotine Inhalator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Change in Salivary Cotinine Levels After 24-hour Use.
Description	Cotinine is a measure sensitive enough to detect effects of a switch to different nicotine products and salivary cotinine was shown to be dependent on nicotine mouth exposure. The results show the mean change in salivary cotinine in each study arm (all study participants).
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Reporting group

Arm/Group Title	Electronic Cigarette	Nicotine Inhalator
Arm/Group Description	All study participants. We analysed 15 brands of the most popular E-Cs in the UK, EU and US for nicotine levels in the mist. Vapours were generated from cartridges of various nicotine content using a standard single-port linear smoking machine with a puff volume of 70 ml, 1 puff every 7 sec., and a puff duration of 1.8 sec (based on averaged puffing conditions from 10 E-C users found during preliminary studies). Nicotine was absorbed in two sequential washing bottles with methanol and internal standards and analysed with gas chromatography. One brand was selected for this study as it consistently delivers about 1mg of nicotine with 20 puffs. Nicotine: Inhalation of nicotine.	All study participants. The inhalator consists of a nicotine cartridge which is placed into a plastic mouthpiece. One cartridge contains 10mg of nicotine of which 4mg of nicotine can be extracted. Nicotine is delivered mainly through the oral cavity, throat, and upper respiratory tract with a minor fraction reaching the lungs. A single cartridge can be used for one 20-minute period of continuous puffing or periodic use of up to 400 puffs per cartridge. Nicotine: Inhalation of nicotine.
Measure Participants	49	49
Mean (Standard Deviation) [ng/ml]	-66.32 (94.84)	-53.8 (119.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Electronic Cigarette, Nicotine Inhalator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Reinforcing Effects of Smoking
Description	Modified Cigarette Evaluation Questionnaire (mCEQ): Measure of reinforcing effects of smoking (pleasant feeling). Mean pleasant feeling from using product (rating 0-4). Higher value indicating the higher rating of pleasure.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Reporting group

Arm/Group Title	Electronic Cigarette	Nicotine Inhalator
Arm/Group Description	All study participants.	All study participants.
Measure Participants	51	51
Mean (Standard Deviation) [units on a scale]	2 (1.11)	0.67 (0.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Electronic Cigarette, Nicotine Inhalator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Airway Sensations
Description	Sensory effects: Measure of airway sensations (throat and chest). Mean enjoyment score (rating 0-4), higher the score indicating increased enjoyment.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Reporting group

Arm/Group Title	Electronic Cigarette	Nicotine Inhalator
Arm/Group Description	All study participants.	All study participants.
Measure Participants	51	51
Mean (Standard Deviation) [units on a scale]	1.65 (1.05)	0.51 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Electronic Cigarette, Nicotine Inhalator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	Product Satisfaction
Description	Product satisfaction: Ratings of product satisfaction (when compared to cigarettes). Rating 0-4, with higher value indicating higher satisfaction ratings.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Reporting group

Arm/Group Title	Electronic Cigarette	Nicotine Inhalator
Arm/Group Description	All study participants.	All study participants.
Measure Participants	51	51
Mean (Standard Deviation) [units on a scale]	1.18 (1.05)	0.59 (1.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Electronic Cigarette, Nicotine Inhalator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	24 hours after product use
Adverse Event Reporting Description	Adverse effects questionnaire (adapted from Hajek et al, 1989)
Arm/Group Title	Electronic Cigarette		Nicotine Inhalator
Arm/Group Description	All study participants used product.		All study participants used product.
All Cause Mortality
	Electronic Cigarette		Nicotine Inhalator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/51 (0%)
Serious Adverse Events
	Electronic Cigarette		Nicotine Inhalator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/51 (0%)
Other (Not Including Serious) Adverse Events
	Electronic Cigarette		Nicotine Inhalator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/51 (58.8%)		34/51 (66.7%)
Cardiac disorders
Dyspnoea	8/51 (15.7%)	8	6/51 (11.8%)	6
Dyspnoea at rest	5/51 (9.8%)	5	2/51 (3.9%)	2
Chest pain	6/51 (11.8%)	6	4/51 (7.8%)	4
Chest discomfort	7/51 (13.7%)	7	3/51 (5.9%)	3
Eye disorders
Visual impairement	4/51 (7.8%)	4	2/51 (3.9%)	2
Gastrointestinal disorders
Nausea	7/51 (13.7%)	7	11/51 (21.6%)	11
Nervous system disorders
Dizziness	9/51 (17.6%)	9	9/51 (17.6%)	9
Headache	10/51 (19.6%)	10	9/51 (17.6%)	9
Sleep disturbance	7/51 (13.7%)	7	5/51 (9.8%)	5
Psychiatric disorders
Disturbances in attention	9/51 (17.6%)	9	15/51 (29.4%)	15
Respiratory, thoracic and mediastinal disorders
Wheezing	7/51 (13.7%)	7	8/51 (15.7%)	8
Cough	14/51 (27.5%)	14	18/51 (35.3%)	18
Productive cough	12/51 (23.5%)	12	9/51 (17.6%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.